CV6-168 is a first-in-class, specific, oral small molecule inhibitor of dUTPase, developed to work in combination with standard chemotherapies that block DNA synthesis in cancer cells — known as thymidylate synthase (TS) inhibitors, such as 5-FU and pemetrexed.
TS inhibitors work by depleting thymine (T), one of the four essential DNA building blocks (A, T, C, and G). Without thymine, cancer cells cannot replicate their DNA properly, halting their growth. However, many cancers develop resistance — either by bypassing the blockade or evolving over time — limiting the effectiveness of these cornerstone therapies.
CV6-168 is designed to overcome this limitation by transforming the way TS inhibitors work. Instead of simply starving the cancer cell of thymine, CV6-168 blocks the enzyme dUTPase, leading to a buildup of uracil — a base not normally found in DNA. When TS inhibitors deplete thymine, the cancer cell mistakenly incorporates uracil into its DNA. This triggers extensive repair attempts by the cell’s own machinery, leading to uracil-induced DNA damage it results in cancer cell death and innate immune system activation.
This novel mechanism exploits the vulnerabilities of rapidly dividing cancer cells — which lack the normal safeguards of healthy tissue — offering a smarter, more effective way to kill tumor cells while preserving tolerability.
CV6-168 is currently in a Phase 1a clinical trial in the UK. Learn more about the Phase 1a trial here: CV6-168 Phase 1a.
